Aberrant p53 expression in metastatic lymph nodes is a significant predictor of recurrence in stage IIIC endometrial cancer

In endometrial cancer (EC), lymph node (LN) metastasis significantly impacts prognosis. In this study, the clinicopathological and molecular characteristics of 33 patients with EC with regional LN metastasis (FIGO stage IIIC) were investigated. We evaluated the mutational status of p53 and DNA mismatch repair (MMR) proteins in positive LNs (102 lesions), mutational variation between primary and paired metastatic lesions, inter-lesion heterogeneity in the metastatic lesions, and their association with clinical outcomes. Immunohistochemically, 13 patients (39.4%) displayed aberrant p53 expression in metastatic lesions, and a concordant rate of 93.4% was found between the primary and metastatic lesions. Genetic diversity between primary and metastatic lesions and among metastases was validated by evaluating p53 and MMR proteins. In Kaplan–Meier analysis, patients with aberrant p53 expression in metastatic LNs exhibited worse progression-free survival (PFS) than those with wild-type expression (p=0.024). Aberrant expression of p53 in the primary lesion did not show a significant difference in PFS compared with wild-type expression. In Cox univariate analysis, only p53 expression in metastatic LNs was significantly associated with recurrence (p=0.031). In conclusion, p53 expression in metastatic LNs is an independent and superior predictor of PFS in patients with EC with regional LN metastasis.